3654
Acknowledgments. The support of the U. S. Public Health Service (Grant G M 10449) is most gratefully acknowledged. We particularly thank Professor Brian Reid for providing laboratory facilities for some of this work.
Eu/IRNA
5
3
I
J. M. Wolfson, D. R. Kearns* Department of Chemistry, University of California Riverside, California 92502 Received February I , 1974
100
50
150
[tRNA1 pM
Figure 2. Effect of E. coli tRNA*Met on the fluorescence decay of M E u 3 + in DtO. The curves depict the variation in the integrated intensities, 10, for the short (rS = 0.8-1.3 msec) and the long lived (78 = 1.95 msec) contributions to the decay. (See text.) These curves show that the maximal contribution from the shortlived component occurs for a Eu3+/tRNAratio of 3: 1.
A General Ketone Synthesis.’ Reaction of Organocopper Reagents with S-Alkyl and S-Aryl Thioesters Sir : Among the more useful organometallic reagents in synthetic chemistry are the organocopper(1) complexes. 2 We now wish to report our results for the reaction of organocopper(1) complexes with S-alkyl and S-aryl thioesters (eq 1-3) which gives ketones in high yield
-
+ R’COSR” R’COR RMgX.CuI + R’COSR“ +R’COR (RCu),. LiI + R’COSR” +R’COR l/zRzCuLi
are useful in interpreting these data. The excitation spectrum of the Eu3+luminescence, obtained with Eu3+/ tRNA ratios of 1 : 1 and 3 : 1, shows a very large peak at 340 nm corresponding to the maximum in the 4-thiouridine absorption but a minimum in the Eu3+ ion absorption. Very little emission (factor of over 100 smaller) was produced by direct excitation of the Eu3+ at 395 nm. When Mgz+was added to the solution conM ) and tRNA ( 5 X M ) the Eu3+ taining Eu2+ luminescence was suppressed but a large excess (0.08 M ) was required to significantly reduce the intensity. On the basis of these observations we draw the following conclusions regarding the binding of Eu3+ E. coli tRNAfMet. (1) There are at least two different types of strong Eu3+binding sites, and this is indicated by the observation of more than one emission lifetime. (2) The exchange of Eu3+between the two different types of binding sites is slow compared with 1.9 msec; otherwise only a single exponential decay would have been observed. (3) The number of strong binding sites is approximately three. (4) The binding of Eu3+ is much stronger than the binding of Mg2+. (5) The very large enhancement of both the short and long-lived components is due to 4-thiouridine sensitized energy transfer and this is confirmed by the excitation spectrum. Since this type of energy transfer is extremely short ranged, at least two of the Eu3+binding sites are located very close (within 5-10 A) to the 4-thiouridine residue at position 8 in E . coli tRNA (see insert, Figure 1J6-l0 These preliminary studies illustrate, but by no means exhaust, the different ways in which rare earth ions may be used to probe metal binding sites on tRNA. Perhaps the most significant result is that there are two strong binding sites located near the 4-thiouridine residue at position 8 and it is interesting to note that the nmr experiments indicate a similar location for a Eu3+ binding site in yeast tRNAPhe.5 (6) A. Heller and E. Wasserman, J . Chem. Phys., 42, 949 (1965). (7) S. I . Weissman, J . Chem. Phys., 10, 214 (1942). (8) P. Yuster and S. I. Weissman, J. Chem. Phys., 17, 1182 (1949). (9) S. I . Weissman, J . Chem. Phys., 18, 1258 (1950). (10) A. Lamola and J. Eisinger in “Molecular Luminescence,” E. Lim, Ed., W. A. Benjamin, New York, N. Y., 1969, p 801.
(1) (2) ( 3)
with efJjcient utilization of organometallic reagent. This reaction appears to be general in scope (Table I). The reaction of S-ethyl decanethioate (1) with various organometallic reagents was examined in some detail (eq 4). Treatment of 1 with either 1 equiv of n-butylRM
+
CH3(CH&COSCHzCHa +CH~(CHZ)~COR 1
magnesium bromide (0”) or 1 equiv of n-butyllithium (-78”) gave the tertiary carbinol 3 (R = n-Bu) and recovered 1 in about equal amounts; lower reaction temperatures did not increase ketone formation from 1 and the Grignard reagent.4 However, when 1 re(1) Contribution No. 18 from the Research Laboratory of Zoecon Corporation. (2) (a) G. H. Posner, Org. React., 19, 1 (1972); (b) J. F. Normant, Synthesis, 4, 63 (1972). (3) Icetones have been prepared, in variable yields from acid chlorides and excess organocuprates: (a) G. M. Whitesides, C. P. Casey, J. San Filippo, Jr., and E. J. Panek, Trans. N . Y. Acad. Sci., 29, 572 (1967); (b) C. Jallabert, N. T. Luong-Thi, and H. Riviere, Bull. SOC.Chim. Fr., 797 (1970); (c) G. H. Posner and C. E. Whitten, Tetrahedron Lett., 4647 (1970); (d) N. T. Luong-Thi, H. Riviere, J.-P. Begue, and C. Forestier, ibid., 2113 (1971); (e) G. H. Posner, C. E. Whitten, and P. E. McFarland, J. Amer. Chem. SOC.,94, 5106 (1972); see also ref 5; (f) N. T. Luong-Thi, H. Riviere, and A. Spassky, Bull. SOC. Chim. Fr., 2102 (1973); from acid chlorides and Grignard derived organocopper(1) complexes, (g) J.-E. Dubois and M. Boussu, Tetrahedron Lett., 2523 (1970); (h) N. T . Luong-Thi and H . Riviere, ibid., 587 (1971); (i) J.-E. Dubois, M. Boussu, and C. Lion, ibid., 829 (1971); (j) J. A . MacPhee and J.-E. Dubois, ibid., 467 (1972); see also ref 3d and 3f; from acid chlorides and 1 : 1 CuX.RLi complexes, (k) H. Gilman and J. M. Straley, Recl. Traa. Chim. Pays-Bas, 55, 821 (1936); (I) A. E. Jukes, S. S. Dua, and H. Gilman, J . Organometal. Chem., 21, 241 (1970); (m) J. F. Normant and M. Bourgain, Tetrahedron Lett., 2659 (1970); (11) M. Bourgain and J. F. Normant, Bull. SOC.Chim. Fr., 2137 (1973); from carbon monoxide and organocuprates; (0)J. Schwartz, Tetrahedron Lett., 2803 (1972); and from certain esters and organocuprates, (p) S. A. Humphrey, J. L. Herrmann, and R. H. Schlessinger, Chem. Commun., 1244 (1971); (9)G. H. Posner and D . J. Brunelle, J. Chem. Soc., Chem. Commun., 907 (1973). (4) Cf.M. S. Newman and A. S. Smith, J . Org. Chem., 13, 592 (1948); for ureaaration of ketones from acid anhydrides and Grignard reagents at 1 7 8 0 .
Journal of’the American Chemical Society 1 96:11 1 M a y 29, 1974
3655 Table I -Product Thioester CH3(CH2)gCOSEte,d
CHs(CH2)gCOSPh CH3COSEt PhCOSEt
Organometallic reagent (equiv) Me2CuLi MelCuLi MetCuLi n-BuMgBrQ n-BuLi (n-Bu)zCuLi (n-Bu)KuLi (n-Bu)zCuLi n-BuLi. CUI n-BuMgBr.Cu1 Ph2CuLi (i-Pr)LhLi (i-Pr)nCuLi MezCuLi (n-Bu)ZCuLi (n-Nonyl)nCuLi (n-Nonyl)2CuLi
(0.55) (1.1) (1.2) (1 .O) (1 .O) (0.55) (1 .O) (1.1) (1 . l ) (1.5) (1.2) (1.1) (1.1) (1.1) (1.0) (0.7) (0.7)
Reaction conditionsD Solvent, Temp, Time ("C) EtZO, - 10, 2 hr EtlO, -10, 10 min EtzO, -78, 2 hr E g o , 0, 0.5 hr Et20, -78, 0.5 hr EhO, -40, 2.5 hr Et20, -40, 2 hr THF, -40, 1.5 hr Et20, -40 to 0, 20 hr THF, -20, 2 hr Et20, -40, 1.5 hr THF, -40, 4 hr EtnO, -40, 5 hr EtzO, -78, 1 hr EtzO, -40, 1 hr Et20, -40, 1.5 hr EtzO, -40, 1.5 hr
Ketone CHs(CH&.COR
(zyie1db)-
-
ReAlcohol covered CHd CH2)aC(OH)Ra thioester
R = Mec(37)' R = Me(51)' R = Me (75)V R = ~I-BUC,' (89) R = n-Bu (87) R = n-Bu (83) R = n-Bu (78)h R = n-Bu (83) R = Phctj (74)" R = i-Prc (66) R R R R
= = = =
Me(72)6 n-Bu (88) Me (61)' Ph(86)'
R = n-Buc (50)h R = ~ - B u(50)h
(Solh
(22)h
( 100)
The thioester was added rapidly to the preformed copper(1) reagent. Reactions were quenched at the stated temperature by dropwise addition of aq NH,Cl. * Yield after distillation unless otherwise noted. c Satisfactory infrared, nmr, and mass spectral analyses were obtained. All thioesters in this report were prepared in essentially quantitative yield from the corresponding acid chloride and 1 equiv of thiol in ether in the presence of 1 to 2 equiv of pyridine. The acid chloride from which 4 was prepared is described by C. A. Henrick, G. B. Staal, and J. B. Siddall, J . Agr. Food Chem., 21,354 (1973). e Yield after preparative tlc and distillation. f Only a trace of aldol could be detected. CJ the reaction of S(2-pyridyl) thioates with Grignard reagents to give ketones: T. Mukaiyama, M. Araki, and H. Takei, J. Amer. Chem. SOC.,95,4763 (1973). * Yield by glpc analysis. * Mp 25-26" (lit. mp 25.5-26"-: V. I. Komarewsky and J. R. Coley, J. Amer. Chem. SOC.,63, 3269 (1941)). 1 Mp 34.5-35.5" (lit. mp 34.4-35.4": F. L. Breusch and M. Oguzer, Chem. Ber., 87,1225 (1954)). Q
acted with lithium di-n-butylcuprate, tertiary carbinol formation was completely suppressed and a high yield of the ketone 2 (R = n-Bu) was obtained. Of special 3.5 hr synthetic significance is the stoichiometric require4 ment of only 1 equiv of R (eq 1) for this conversion. Thus, reaction of 1 in diethyl ether with either 0.55 or 1.0 equiv of lithium di-n-butylcuprate gave similar yields of 5-tetradecanone. Essentially complete 5 utizization of both the alkyl groups of the organocuprate 6 E and 4 2 , 6 E isomers in the ratio (3 :I), can be carried complex is therefore possible, in marked contrast to out by the use of 2 equiv of lithium diethylcuprate in the results obtained from reaction of organocuprates tetrahydrofuran at -45 '. Further addition of lithium with acid chlorides where 3 equiv of R,CuLi (6 equiv of R) are required for optimal yields of ketones.3e diethylcuprate to the dienone 5 is not a significant under these conditions, but the perproblem (
